Oral Antifungal Agents Research Articles

A cost-effectiveness analysis of the use of oral ibrexafungerp versus fluconazole for acute vulvovaginal candidiasis in the UK NHS primary care service.

Vulvovaginal Candidiasis (VVC) is a fungal infection causing inflammation of the vagina and/or the vulva. Symptoms include itching, irritation, and discharge. VVC presents commonly across primary care and, despite its mild symptoms, carries psychological burden and has a significant impact on women's quality of life. UK guidelines support treatment via oral or topical azole antifungal agents. Recent evidence attests to the superiority of novel non-azole antifungals. Thus, rigorous financial assessment of both antifungals is necessary for optimal VVC treatment allocation in UK primary care. To evaluate the cost-effectiveness of ibrexafungerp against the gold standard fluconazole as first-line treatment of VVC within the NHS. A systematic review on the efficacy of ibrexafungerp and fluconazole in acute VVC was conducted. Cost-effectiveness analysis was initiated using health outcome data from the DOVE trial, a Phase 2 RCT. Costs in pound sterling were ascertained in monetary units, and effectiveness determined as reduced need for follow-up medication. An incremental cost-effectiveness ratio of £2185.74 was determined. This suggests oral ibrexafungerp being largely more costly yet slightly more effective than fluconazole, and thus has unfavourable net benefit. Two sensitivity analyses were conducted considering follow-up medication combination and market price, which provided confidence in the calculated cost-effectiveness ratio. This analysis highlights fluconazole's cost-effectiveness in current UK guidelines and favourability.

Comprehensive Review of Tinea Capitis in Adults: Epidemiology, Risk Factors, Clinical Presentations, and Management.

Tinea capitis is a fungal infection of the scalp and hair caused by dermatophyte molds, that most often affects children and may also affect adults. Previous estimates suggest that between 3% and 11% of all tinea capitis cases worldwide occur in adults, although updated epidemiological studies are needed to reassess the prevalence of tinea capitis in adult populations specifically. Postmenopausal adult women are most often affected by tinea capitis, with African American or Black women particularly at risk. Adults who experience crowded living conditions, who live in close proximity to animals, who are immunosuppressed, and/or who live in households with affected children are at greatest risk of infection. Tinea capitis can be non-inflammatory or inflammatory in nature, and the subtype affects the extent and severity of clinical symptoms. Fungal culture and potassium hydroxide preparations are the most commonly used diagnostic tools. Trichoscopy, defined as dermoscopic imaging of the scalp and hair, is a useful adjunct to the physical examination. The mainstay of therapy is oral antifungal therapy, and topical therapy alone is not recommended. Since tinea capitis infection is uncommon in adults, there are no widely accepted treatment guidelines. Rather, the same medications used for tinea capitis infection among children are recommended for adults at varying doses, including griseofulvin, and terbinafine, and, less commonly, itraconazole and fluconazole. The prognosis for tinea capitis in adults is typically excellent when prompt and adequate treatment is administered; however, delayed diagnosis or inadequate treatment can result in scarring alopecia. Over the past decade, dermatophyte infections resistant to treatment with topical and oral antifungal agents have emerged. While tinea capitis infections resistant to antifungal therapy have been rarely reported to date, antifungal resistance is rising among superficial fungal infections in general, and antifungal stewardship is necessary to ensure that resistance to treatment does not develop among dermatophytes that cause tinea capitis.

Failed Treatment of Multidrug-resistant Acinetobacter Baumannii Keratitis Mistaken for a Mixed Infection

Purpose: To report treatment failure of multidrug-resistant <i>Acinetobacter baumannii</i> keratitis in a patient wearing contact lenses for a long time.Case summary: A 48-year-old man using daytime soft lenses for 20 years was transferred due to decreased visual acuity and eye pain. Slit-lamp biomicroscopy showed a large corneal epithelial defect and stromal infiltration, but no hypopyon. Treatment was initiated with moxifloxacin, polyhexamethylene biguanide eye drops, and oral antibiotics. Corneal infiltration worsened, corneal scrapings and culture were performed. Gram staining showed Gram-positive bacteria, potassium hydroxide (KOH) hyphae-positive, and culture yielded Bacillus. He was hospitalized and vancomycin, voriconazole, and amphotericin B eye drops were administered. Oral antifungal agents were also prescribed. The corneal epithelial defect was restored from temporal side for a while, and then deteriorated with an endothelial plaque. Therefore, voriconazole and amphotericin B were injected intracamerally. All four repeated culture tests were negative. Despite total conjunctival flap, the patient complained of severe pain and eventually underwent evisceration. In the culture of intraocular contents, <i>Acinetobacter baumannii</i>, which is resistant to all drugs except minocycline, was detected.Conclusions: In patients wearing contact lens for a long time, not only mixed infection with acanthamoeba and fungi, but also gram-negative bacteria should be considered first, and multidrug-resistant <i>Acinetobacter baumannii</i> should also be considered.

Sporotrichosis from a tertiary care hospital in the Eastern State of India

Sporotrichosis is a form of subcutaneous or systemic fungal infection caused by Sporothrix schenkii. This is a thermophilic, dimorphic fungus that occurs worldwide in tropical and temperate areas. We report a case series of sporotrichosis in three patients from a tertiary care center in Assam. The source of infection could be identified in each patient. The patients were successfully treated with oral and topical antifungal agents, which included capsule Itraconazole and supersaturated potassium iodide therapy.

Antimicrobial surveillance in South Australian prisons: a pilot study.

ObjectivesThis study aimed to determine the feasibility of capturing antimicrobial usage data from prisons for inclusion in the Antimicrobial Use and Resistance in Australia (AURA) surveillance system and to analyse 2021 and 2022 South Australian (SA) usage data for notable trends.MethodsMonthly antimicrobial supply data for eight SA prisons were collected. Antimicrobial volume was converted into the World Health Organization metric, defined daily doses (DDD). Usage rates were calculated relative to prison occupied bed days (OBD).ResultsAnnual usage of systemic antimicrobials across eight SA prisons totalled 26,448 DDD and 23,526 DDD in 2021 and 2022 respectively. Antibacterials accounted for 80.6% of all antimicrobials dispensed during the study period. The average antibacterial usage rate in female prisons was higher on average than in male prisons. The state-wide systemic antibacterial usage rate in SA prisons declined by 11.3% from 23.8 DDDs/1000 OBD in 2021 to 21.1 DDDs/1000 OBD. Doxycycline, amoxicillin, flucloxacillin, amoxicillin-clavulanic acid, and cefalexin accounted for 72% of the total systemic antibacterial usage rate. Variation in the oral and topical antifungal agents used and the rate of use was observed between prisons.ConclusionsThis SA pilot study demonstrates the feasibility of including prisons in routine national antimicrobial surveillance using similar methodology to hospital surveillance. The contributing facilities comprised 6.1% of all Australian prison beds, and extrapolation of the results suggests that the identified gap in surveillance may equate to over 400,000 DDD per annum in prisons nationwide, equating to approximately 5% of hospital inpatient antimicrobial usage.

Efficacy of super bioavailable itraconazole in the management of dermatophytosis in India

Itraconazole (ITZ) is a commonly prescribed oral antifungal agent in India and has a low minimum inhibitory concentration when compared to other oral antifungals. However, clinicians have reported inconsistent clinical responses despite its high skin levels, which may be due to variations in pelletization parameters, which affect its bioavailability and serum levels. Conventional ITZ has a maximum bioavailability of 55%; however, this is unpredictable and inconsistent. In contrast, the novel ITZ formulation, super bioavailable ITZ (ITZ-SB), has targeted drug release in the small intestine, resulting in predictable serum levels with minimal interindividual variability. This makes it a potentially useful drug in treating recalcitrant dermatophytosis. This expert opinion highlights the benefits of novel ITZ-SB with the incorporation of SUBA® technology. The SUBA® technology improves the bioavailability of poorly soluble drugs by ‘solid dispersion’ in polymer to increase drug absorbency. This technology also has potential to reduce variability in absorption and adverse effects. Benefits of this technology include more predictable clinical response and lower drug quantities necessary to achieve therapeutic blood levels, making it a promising treatment option for recalcitrant dermatophytosis. Fixtral SB, which uses this technology, is a novel weapon in the arsenal of treatments for superficial mycoses.

Tinea pedis: an updated review.

Tinea pedis is one of the most common superficial fungal infections of the skin, with various clinical manifestations. This review aims to familiarize physicians with the clinical features, diagnosis and management of tinea pedis. A search was conducted in April 2023 in PubMed Clinical Queries using the key terms 'tinea pedis' OR 'athlete's foot'. The search strategy included all clinical trials, observational studies and reviews published in English within the past 10 years. Tinea pedis is most often caused by Trichophyton rubrum and Trichophyton interdigitale. It is estimated that approximately 3% of the world population have tinea pedis. The prevalence is higher in adolescents and adults than in children. The peak age incidence is between 16 and 45 years of age. Tinea pedis is more common amongst males than females. Transmission amongst family members is the most common route, and transmission can also occur through indirect contact with contaminated belongings of the affected patient. Three main clinical forms of tinea pedis are recognized: interdigital, hyperkeratotic (moccasin-type) and vesiculobullous (inflammatory). The accuracy of clinical diagnosis of tinea pedis is low. A KOH wet-mount examination of skin scrapings of the active border of the lesion is recommended as a point-of-care testing. The diagnosis can be confirmed, if necessary, by fungal culture or culture-independent molecular tools of skin scrapings. Superficial or localized tinea pedis usually responds to topical antifungal therapy. Oral antifungal therapy should be reserved for severe disease, failed topical antifungal therapy, concomitant presence of onychomycosis or in immunocompromised patients. Topical antifungal therapy (once to twice daily for 1-6 weeks) is the mainstay of treatment for superficial or localized tinea pedis. Examples of topical antifungal agents include allylamines (e.g. terbinafine), azoles (e.g. ketoconazole), benzylamine, ciclopirox, tolnaftate and amorolfine. Oral antifungal agents used for the treatment of tinea pedis include terbinafine, itraconazole and fluconazole. Combined therapy with topical and oral antifungals may increase the cure rate. The prognosis is good with appropriate antifungal treatment. Untreated, the lesions may persist and progress.

Outcome of fosravuconazole treatment for onychomycosis refractory to topical antifungal agents.

Fosravuconazole L-lysine ethanolate (F-RVCZ) is an oral antifungal agent approved in Japan for the treatment of onychomycosis. We treated 36 patients (mean age 77.6 years) with onychomycosis that had been refractory to long-term topical treatment. The patients took F-RVCZ (100 mg ravuconazole) once daily for a mean of 11.3 weeks, and were followed up for an average of 48 weeks (mean 48.3 ± 2.1 weeks). The mean rate of improvement of the affected nail area at 48 weeks was 59.4%, and 12 patients achieved complete cure. Patients with total dystrophic onychomycosis (TDO) showed a significantly lower improvement rate than those with distal and lateral subungual onychomycosis (DLSO), and those with an affected nail area of 76%-100% at the first visit showed a significantly lower improvement rate than those with an affected nail area of 0%-75%. Six patients had adverse events necessitating treatment discontinuation, but the symptoms and laboratory data improved without specific treatment in all of them. The data suggest that F-RVCZ would be effective in various age groups, including the elderly, and even in patients with onychomycosis refractory to long-term topical antifungal treatment. It was also suggested that its early use in mild cases might achieve a higher rate of complete cure. Furthermore, the average cost of oral F-RVCZ therapy was lower than that for topical antifungal agents. Therefore, F-RVCZ is considered to be much more cost-effective than topical antifungal agents.

Histoplasmosis of the External Auditory Canal

This report describes the diagnosis and treatment of a patient with a rare fungal infection of the external ear, as well as a review of the literature. A 76-year-old Caucasian gentleman from rural southern United States with diabetes and hypertension was referred to our clinic for intractable left otalgia, otorrhea, headaches, and an exophytic lesion in the left external ear since five months. There was no pertinent travel history. Biopsy by an outside otolaryngologist was inconclusive. Repeat biopsy under anesthesia revealed morphological characteristics consistent with histoplasmosis. Intravenous amphotericin B and later oral antifungal agent voriconazole led to improvement in symptoms. The clinical presentation resembled a malignancy. A high index of clinical suspicion, histologic confirmation with deep tissue biopsy, and culture are essential for diagnostic confirmation followed by treatment with systemic antifungals. A multidisciplinary team approach is necessary to manage this rare condition.

Allergic Fungal Rhinosinusitis: The Role and Expectations of Biologics

Allergic fungal rhinosinusitis (AFRS) is a noninvasive subtype of chronic rhinosinusitis with nasal polyps (CRSwNP) that usually develops in immunocompetent atopic individuals and is more common in geographic regions characterized by warm temperatures and high humidity, conducive to higher environmental fungal presence. Allergic fungal rhinosinusitis usually presents with unique computed tomography findings and significant polyp burden, yet patients often report minimal sinus symptoms. Patients with AFRS often have extremely elevated serum total and fungal-specific IgE levels. Treatment almost always requires surgery, in which adjuvant medical therapy is critical to success. However, until recently the choice of adjuvant therapy has consisted primarily of either oral and/or topical steroids. Although oral corticosteroids decrease recurrence after surgery, data for the effectiveness of other adjunctive pharmacologic agents, including topical and oral antifungal agents and immunotherapy, have remained unclear and hence are not recommended in recent guidelines including the International Consensus of Allergy and Rhinology. Three biologics, omalizumab, dupilumab, and mepolizumab, have recently been approved for treating CRSwNP in general, but clinical trials to date with these biologics did not involve AFRS patients. Recently published case reports and smaller prospective studies have shown good efficacy of these biologics on the AFRS subgroup of patients. This article provides an overview of the understanding of the pathophysiology of AFRS, implications of this understanding on the possible role of biologics, and clinical reports on the use of biologics in treating AFRS. Because biologics are indicated for treating CRSwNP, follow up real-world evidence studies are needed for AFRS.

Vulvovaginal candidiasis: Epidemiology, treatment and prevention strategies

Vulvovaginal candidiasis (VVC) is a commonly encountered clinical condition. At least three-fourth women experience one episode of VVC in their lifetime. In India, the prevalence of VVC is 10 to 35%. Laboratory methods often supplement clinical diagnosis. VVC should be confirmed with culture and other investigative techniques, especially in complicated and recurrent cases. Topical and intravaginal azoles remain the mainstay of therapy. In women who have predisposing risk factors or develop recurrent VVC, oral antifungal agents are used. Topical steroids may be used in women having vulvar symptoms along with pruritus. Pregnancy is a significant risk factor. Intravaginal azoles remain the standard of treatment and can be offered from the second trimester onwards. The emergence of non-albicans species has caused difficulties in the management of VVCs. Thus, all women with vaginal discharge should be correctly diagnosed to tailor the therapy.

Impact of Composition and Morphology of Ketoconazole-Loaded Solid Lipid Nanoparticles on Intestinal Permeation and Gastroplus-Based Prediction Studies.

Ketoconazole (KTZ) is a potential oral antifungal agent to control systemic and local infections. This study addresses the impact of composition (tween 80 and compritol as CATO) and morphology on permeation (stomach, jejunum, and ileum) profiles of KTZ-loaded solid lipid nanoparticles (SLNs) in rats followed by in vivo pharmacokinetic prediction and simulation using GastroPlus. The selected formulations were characterized for size, size distribution, zeta potential, entrapment efficiency, total drug content, morphology, in vitro drug release, ex vivo permeation and drug deposition, penetration potential, and GastroPlus-based in vivo prediction in rats. The results showed that there was considerable impact of pH, composition (CATO and tween 80), size, total drug content, and entrapment efficiency on in vitro drug release and permeation across the stomach, jejunum, and ileum. Ex vivo findings suggested pH, composition, size, and permeability coefficient-dependent permeation of SLNs across the stomach, jejunum, and ileum. Confocal laser scanning microscopy (CLSM) confirmed a relatively high degree of penetration of the optimized formulation “K-SLN4” (66.1% across the stomach, 51.5% across the jejunum, and 47.9% across the ileum) as compared to KSUS (corresponding values of 21.7%, 18.2%, and 17.4%). Finally, GastroPlus predicted in vivo dissolution/absorption as 0.012 μg/mL of K-SLN4 as compared to KSUS (the drug suspension with 0.0058 μg/mL) and a total regional absorption of 80.0% by K-SLN4 as compared to 60.1% of KSUS. There was only an impact of dose on Cmax (maximum plasma concentration) and area under the curve (AUC) in rats. Thus, the present strategy could be a promising alternative to parenteral and topical delivery systems for long-term therapy against systemic and local mycoses with high patient compliance.

Efficacy and Safety of Prophylactic Antifungal Agents in Preventing Invasive Fungal Infection and Mortality among Infants Weighing Less than 1500 Grams: A Meta-analysis

Background. Preterm infants with very low birth weight are at increased risk of invasive fungal infections. Preventive strategies are needed to improve their clinical course and survival.
 Objectives. To assess the efficacy and safety of antifungal agents as prophylaxis in controlling invasive fungal infection and mortality in very low birth weight (VLBW) and extremely low birth weight (ELBW) infants in neonatal intensive care units.
 Methods. We searched MEDLINE (PubMed), Cochrane databases, Google Scholar, Trip database, Herdin, and ClinicalTrials.gov without language restriction and publications from January 1988 to May 2021. We included randomized controlled trials or controlled clinical trials that compared the effect of prophylactic oral or systemic antifungal agents versus placebo in preterm infants < 37 weeks age of gestation and with birth weight lower than 1500 grams. We conducted a meta-analysis using RevMan 5.4.1 and certainty of evidence rating using GRADEpro software.
 Results. A total of 14 studies (including 3,001 preterm infants with VLBW) were included. We found that prophylactic use of nystatin significantly reduced the incidence of invasive fungal infections (IFI) (pooled RR 0.16; 95% CI 0.11, 0.23; 4 RCTs, N = 1295; P < 0.00001; moderate certainty evidence) in preterm infants compared to placebo but had no significant effect on the mortality (RR 0.87; 95% CI 0.62, 1.23; 4 RCTs, N = 1295; P = 0.43; low certainty evidence). Similarly, fluconazole decreased the incidence of IFI (RR 0.38; 95% CI 0.28, 0.53; P = 0.02) and showed statistically significant reduction in mortality (RR 0.78; 95% CI 0.61, 0.99; RCTs, N = 1484; P = 0.04; high certainty evidence). The comparison of the two antifungals showed a trend favoring fluconazole, however the difference was not statistically significant in decreasing IFI (RR 1.60; 95% CI 0.68, 3.77; P = 0.28) and mortality (RR 1.62; 95% CI 0.76, 3.45; P = 0.21).
 Conclusion. Administration of antifungal prophylaxis proves to be beneficial and can probably decrease invasive fungal infection and mortality. The evidence showed that Fluconazole is superior as antifungal prophylaxis compared to placebo while there is no significant difference between fluconazole and nystatin in decreasing fungal infection and mortality among preterm neonates.

Ibrexafungerp in the Treatment of Vulvovaginal Candidiasis.

To review the pharmacology, efficacy, and safety of ibrexafungerp in the management of vulvovaginal candidiasis (VVC). Literature was sought using PubMed (1966-February 2022) and EMBASE (1973-February 2022), and clinicaltrials.gov. Search terms included ibrexafungerp, SCY-078, and VVC. All studies including humans and published in English with data assessing the efficacy and safety of ibrexafungerp for the treatment of VVC were evaluated. A phase 2 dose-finding study found ibrexafungerp had similar efficacy to fluconazole in the clinical cure of VVC (51.9% vs 58.3%, respectively). Two phase 3 clinical trials demonstrated ibrexafungerp had statistical superiority over placebo for clinical cure in moderate to severe VVC (P < 0.001 and P = 0.023, respectively). The most frequently reported adverse reactions in the clinical trials were gastrointestinal-related symptoms. To date, data comparing efficacy of ibrexafungerp and topical imidazoles in the treatment of VVC are nonexistent. Topical imidazoles and oral fluconazole are effective for the treatment of uncomplicated VVC. Due to increased resistance, limited fluconazole coverage for non-Candida albicans species, and potential for significant drug interactions associated with fluconazole use, alternative treatments for VVC are needed. Ibrexafungerp is a new oral triterpenoid antifungal agent indicated for the treatment of VVC. Additional clinical trials are needed to evaluate long-term safety data as well as efficacy and safety in specialty populations. Ibrexafungerp, a recently approved triterpenoid antifungal agent, is an effective and well-tolerated option for the treatment of VVC.

Development of Innovative Cosmetic Formulations to Help Fungal Treatment and Testing the Efficiency of Formulations

In the fungus of hands and toenails, the thickening of the nail and its yellow color are the first signs of attention. Fungus on the nails of the hands and feet is often caused by Trichophyton rubrum dermatophyte. They have antifungal properties due to the components found in lavender oil, geranium oil and tea tree oil structures. Oral antifungal agents used for treatment of nail fungi have serious side effects especially on liver. Therefore, topical applications have been given importance in recent years. However, in topical applications antifungal agents have difficulties in sending to the target area. For this reason, nanoemulsion technology was preferred in the study. Nanoemulsion formulations of essential oils were prepared using ultrasonication method. Centrifugal and thermal test were applied as preliminary stability to the formulations and the pH value, viscosity, droplet size and polidispersity index of the formulations passing this step were measured and organoleptic controls were performed. Antifungal efficacy and release studies were performed on the formulations F4P3-I (pelargonium), F4P3-L (lavender), F4P3-C (tea tree) and F4P3-K (mixture) which were successful as a result of all the tests. According to the study, it was concluded that F4P3-I, F4P3-L, F4P3-Ç, F4P3-K formulations may help in the treatment of fungi.

A case of Erythroderma following Terbinafine therapy

Background: The onset of cutaneous lupus erythematosus may be associated with the administration of a variety of drugs. Terbinafine, an oral antifungal agent, which rarely causes cutaneous eruptions, has been implicated as the cause or exacerbation of cutaneous lupus erythematosus in several patients. Case: A 52-year-old female patient had received oral terbinafine for onychomycosis. The patient had a family history of lupus, but no personal history. Six weeks after initiating treatment with terbinafine the patient developed cutaneous lupus which was diagnosed clinically and by histology. She developed an erythrodermic rash. Immunological studies showed elevated titres of anti-nuclear antibodies. Following discontinuation of terbinafine therapy and under the treatment of systemic and topical steroids, a slow resolution of the eruption was noted over several weeks. Conclusions: This report, along with previous cases described, suggests the association between terbinafine therapy and the onset or exacerbation of SLE often occurring in a patient with history of systemic lupus erythematosus or SLE. Key words: SLE, erythroderma, drug reactions

Cosmetological competence of nail patches in combating onychomycosis-An approach to improve the quality of life

Onychomycosis (Tinea unguium) is said to be the most common cosmetological nail fungal infection. Dermatophyte is a type of fungus that causes this condition. Discoloration and thickening of the nail are found to be the common symptoms of all nail diseases. In this scenario, Onychomycosis is considered as one of the cosmetic problems that leads to cellulitis in adults and diabetic patients. Anatomical structure of the nail and disease manifestations made nail disorders as a difficult endeavor. Onychomycosis is chronic and difficult to eradicate. Many oral antifungal agents are available for the treatment of nail infections. The oral and parenteral administration of antifungal agents can elevate the serum hepatic enzyme levels and causes typical hepatocellular injury within a few weeks of therapy. The goal of this review is to study the role of transungal delivery systems (nail patches) as a promising tool for onychomycosis to encounter the clinical conditions of the patient. Longer therapies and technical treatment methods may frustrate the patients. This novel antifungal therapy helps to avoid the surgical removal of nail for onychomycosis patients. Eradication of issues with Onychomycosis can be achieved by an excellent delivery system with deeper drug release and drug retention in the nail cuticle. Patients who are suffered from onychomycosis are facing embarrassment and disfigurement in the society. So, this newer treatment solution can improve the quality of life of patients.1-3

Recent Perspectives in the Management of Fungal Keratitis.

Mycotic keratitis is common in warm, humid regions with a varying profile of pathogenic fungi according to geographical origin, socioeconomic status, and climatic condition. Clinical diagnosis can be challenging in difficult cases and those refractory to treatment. Fungal hyphae on microscopic examination and culture isolation have been the gold standard in the laboratory diagnosis of fungal keratitis. A culture isolate of the aetiological fungus is essential to perform antifungal susceptibility testing. As the culture isolation of fungi is time-consuming, causing delays in the initiation of treatment, newer investigative modalities such as in vivo confocal microscopy and molecular diagnostic methods have recently gained popularity. Molecular diagnostic techniques now help to obtain a rapid diagnosis of fungal keratitis. Genomic approaches are based on detecting amplicons of ribosomal RNA genes, with internal transcribed spacers being increasingly adopted. Metagenomic deep sequencing allows for rapid and accurate diagnosis without the need to wait for the fungus to grow. This is also helpful in identifying new emerging strains of fungi causing mycotic keratitis. A custom-tear proteomic approach will probably play an important diagnostic role in future in the management of mycotic keratitis. Positive repeat cultures are being suggested as an important gauge indicative of a poor prognosis. Positive repeat fungal cultures help to modify a treatment regimen by increasing its frequency, providing the addition of another topical and oral antifungal agent along with close follow-up for perforation and identifying need for early therapeutic keratoplasty. The role of collagen crosslinking in the treatment of fungal keratitis is not convincingly established. Rapid detection by multiplex PCR and antifungal susceptibility testing of the pathogenic fungi, adopted into a routine management protocol of fungal keratitis, will help to improve treatment outcome. Early therapy is essential in minimizing damage to the corneal tissue, thereby providing a better outcome. The role of conventional therapy with polyenes, systemic and targeted therapy of antifungal agents, newer azoles and echinocandins in fungal keratitis has been widely studied in recent times. Combination therapy can be more efficacious in comparison to monotherapy. Given the diversity of fungal aetiology, the emergence of new corneal pathogenic fungi with varying drug susceptibilities, increasing the drug resistance to antifungal agents in some genera and species, it is perhaps time to adopt recent molecular methods for precise identification and incorporate antifungal susceptibility testing as a routine.

Comparative evaluation of the efficacy of itraconazole with terbinafine cream versus itraconazole with sertaconazole cream in dermatophytosis: A within person pilot study

BackgroundCurrent trend of rising drug-resistant dermatophyte infection is alarming and fretted by dermatologists. Dilemma prevails regarding use of the same or different class of antifungal agents topically and systemically. The aim was to study the efficacy of oral itraconazole 200 mg with 1% terbinafine cream versus oral itraconazole 200 mg with 2% sertaconazole cream in dermatophytosis. MethodsThis within-person open-label pilot study enrolled 50 patients with dermatophytosis. Two lesions of comparable size within each patient were randomly allotted to group A and B and treated with 2% sertaconazole and 1% terbinafine cream, respectively. Both groups received itraconazole 200 mg once daily for 4 weeks. The remaining lesions received 1% terbinafine cream. Response and adverse effects were assessed at 2 and 4 weeks. Reduction in erythema, scaling, pruritus and clinical, and mycological cure constituted efficacy outcomes. ResultsThe mean duration of lesions was 2.82 ± 1.35 months. Complete clinical cure was observed in 50% and 48%, whereas mycological cure was attained in 56% and 52% patients in groups A and B, respectively, after 4 weeks, which was statistically insignificant. Reduction in erythema, scaling, and pruritus after 4 weeks when compared between the two groups, was also statistically insignificant. ConclusionSame class of oral and topical antifungal agents has comparable efficacy with different classes of oral and topical antifungal agents in dermatophyte infection.

Anti-fungal agents in the treatment of chronic pulmonary aspergillosis: Systematic review and a network meta-analysis.

Oral itraconazole and voriconazole are currently recommended in the initial management of chronic pulmonary aspergillosis (CPA). However, only a few studies have compared outcomes with different anti-fungal agents (AFAs) in treating CPA. Herein, we perform a network meta-analysis comparing the efficacy of different AFAs in CPA. We searched the PubMed and EmBase databases to identify studies (either randomised-controlled trials [RCTs] or observational) reporting treatment outcomes with AFAs in patients of CPA. The study quality was assessed using the Newcastle-Ottawa scale (NOS). We performed a network meta-analysis to compare the relative efficacy of different AFAs in treating CPA. The primary outcome was a favourable response to treatment with AFAs. We found ten studies (718 patients) investigating different AFAs (oral AFAs [n=5], intravenous AFAs [n=5]) in the treatment of CPA. There were four RCTs and six observational studies. The studies using oral agents reported long-term outcomes (>12weeks), while those with intravenous agents provided only short-term outcomes (<6weeks). We found one study of posaconazole and none with isavuconazole for treating CPA. Amongst the oral agents, itraconazole was significantly better than supportive care and was ranked as the best oral AFA on network rank analysis. We found all intravenous AFAs to be equally effective. Intravenous echinocandins and voriconazole were ranked best for achieving a favourable treatment response. Oral itraconazole may be preferred over other azoles as the initial therapy for CPA. Amongst the intravenous agents, echinocandins and voriconazole may be preferred over amphotericin B. Randomised-controlled trials comparing different AFAs, especially the newer AFAs, are urgently needed.